The vaginal ecosystem is a finely balanced environment maintained by a complex interaction among a variety of bacteria, infrequently including yeasts, which all occur naturally in the vagina.
Urogenital infections, including urinary tract infections (UTI), bacterial vaginosis (BV) and yeast vaginitis are common disorders in women all around the world. More than 75% of women will have at least one vaginal infection in their lives, and 50% of these women will have a recurrence of the infection.
Bacterial vaginosis generally shows little or no inflammation of the vaginal epithelium and resembles more of an alteration of the bacterial vaginal environment than a proper infection of tissues or epithelium. BV is currently treated mainly with antibiotics. Antibiotics, however, also kill useful bacteria present in the vaginal environment, such as Lactobacilli, resulting in a pH increase in the vaginal environment and increasing the risk of recurrence of the bacterial vaginosis or the development of a different vaginal infection, such as a yeast infection
The yeast Candida albicans is present in most humans as a harmless commensal organism, but may cause infections, e.g. candidiasis when a person experiences a loss of normal bacterial flora. In severely immune compromised patients, Candida albicans can spread throughout the body and cause deadly systemic infections.
Certain Lactobacillus species are the dominant bacteria in a healthy vaginal ecosystem, and they maintain an acidic environment of the vagina through the production of lactic acid.
Acidity is believed to be one of the protective mechanisms of the vagina. This acidity has been associated with a decreased risk of infections such as chlamydia, genital mycoplasma, trichomoniasis, urinary tract infection and a decreased carriage of bacteria in the introitus (Hanna, N et al 1985, 1975, Stamey T A and Kaufman M F 1975, Stamey T A and Timothy M M 1975).
A favourable environment for the lactate producing microbiota is generally present, and results in a pH of approximately 4 in the mucousal secretions. However, the environment can be disturbed by factors such as variations in the oestrogen concentration during certain periods of the menstrual cycle and during the menopause, and also by an increasing occurrence of secretions of various types, for example from protracted menstrual haemorrhages, premenstrual bloody discharges, mid-cycle bleeding and ejaculate. Foreign bodies in the vagina, for example coils, pessaries and those inserted, for example, in connection with antibiotic treatment and on washing can also lead to a disruption of the healthy microbiota which is such that the pH rises. When the pH rises above 4.5 there is an increased tendency towards growth of anaerobic bacteria.
Bacterial vaginosis is an indication that the defence against infection, which is partly conferred by a low pH, has been weakened and, under unfavourable circumstances, this leads to actual infection.
Shifts in bacterial biota are associated with shifts in vaginal pH (Caillouette J C et al 1997). During BV a shift from being lactobacillus dominated to a biota in which G. vaginalis and anaerobic bacteria predominate is observed. The presence of anaerobic bacteria gives rise to volatile amines at an increased pH (<4.5).
An acidic enviroment is mantained by a Lactobacillus flora which produces lactic acid. In order for this production of lactic acid to be maintained, several attempts have been made to provide a pH reduction to create a favourable environment necessary for protection against infection.
For example, EP 0 257 007 relates to an agent for reinforcing the natural protection mechanisms of the vaginal mucosa by helping to re-establish the productive environment for lactobacteria. The agent comprises lactic acid and a buffering substance in a content such that the pH lies within the range from 3.5 to 4.
A pH below 4 makes it easier for lactobacillus species to recolonize the vagina and thereby restore the natural resistance toward overgrowth by bacteria connected with BV.
EP 1 782 794 relates to an anhydrous composition and to a method of maintaining a healthy vaginal pH to control vaginal odor. The composition may be applied to the vaginal area to lower vaginal pH and assist in maintaining such pH over a period of time.
WO 06/001766 relates to a composition comprising lactic acid and lactoferrin and/or a a peptide fragment thereof for the treatment and/or prophylaxis of conditions in the urogenital tract. The incorporation of lactoferrin or a peptide fragment thereof is proposed to enhance the antimicrobial activity of the composition.
Lactate given in a gel has shown to be effective against bad odour associated with BV (Lactal). The lactate gel has also been shown to have some antibacterial effects against certain BV-associated bacterial species. (see Andersch B et al; Treatment of Bacterial vaginosis with an Acid cream: A comparison between the effect of Lactate gel and Metronidazole″ Gynecol Obstet Invest 21:19-25, 1986).
The lactic acid in the gel lowers the pH level and is effective in preventing malodour which appears during BV.
However, application in the form of a gel is often associated with leakage from the vagina which often requires the use of some form of sanitary protection. This has an impact on patient acceptability and compliance with therapy.
Accordingly, there is a need in the art to find a more efficient local vaginal therapy for treating and/or preventing bacterial vaginosis and/or fungal infections, particularly yeast infections. Ideally, this treatment should be well tolerated, good to handle as well as provide excellent patients' acceptability.